While oral contraceptives have been in widespread use for about 25 years, the effects of these compounds on risk of coronary heart disease (CHD) remain unclear. This is due largely to a lack of basic investigation into effects of estrogens and progestins on the pathogenesis of atherosclerosis and, in the presence of atherosclerosis, clinically relevant vasomotor function. The long-term objective of this project is to determine, using a well- -characterized nonhuman primate model, effects of an estrogen and progestin commonly used in oral contraceptives on the pathogenesis of atherosclerosis and CHD. The specific aims are: 1) To determine the effects of a contraceptive estrogen and progestogen alone, or in combination, on extent of diet-induced coronary artery atherosclerosis; 2) to determine effects of the estrogen and progestogen on functional parameters of early atherogenesis, i.e., LDL uptake and degradation, monocyte adherence to endothelium, endothelial cell turnover; 3) to determine effects of the same steroids on plasma lipoprotein distribution, heterogeneity and composition, and whether steroid induced changes in HDL composition are associated with atherosclerosis extent or influence cholesterol efflux by cultured cholesterol laden monocyte/macrophages; 4) to determine direct effects of the estrogen and progestin administered both in vivo and in vitro on cholesterol efflux by cultured cholesterol laden macrophages; and 5) to determine effects of the steroids on endothelium mediated vascular responses in early and advanced atherosclerosis. The results will provide an important comparative (nonhuman primate) basis for understanding better the effects of exogenous estrogens and progestins on the pathogenesis of CHD and, thus, for establishing approaches to the prevention of CHD in women.